Influenza has a long history characterized by waves of pandemics, epidemics, resurgences and outbreaks. Influenza is a highly contagious disease with the potential to be devastating both in developing and developed countries. In spite of annual vaccination efforts, influenza infections result in substantial morbidity and mortality each year. Although pandemics do not occur very often, flu strains have recently emerged that increase the potential for an influenza pandemic. An example is the avian influenza virus of the type H5N1, which as caused an epidemic in poultry in Asia as well as in regions of Eastern Europe, and has persistently spread throughout the globe. The rapid spread of infection and the cross species transmission from birds to humans has increased the potential for outbreaks in human populations and the risk of a pandemic. The virus is highly pathogenic, with a mortality rate of over fifty percent in birds as well as the few human cases that have been identified. Human to human transmission of the virus would have the potential to result in rapid, widespread illness and mortality.
The major defense against influenza is vaccination. Influenza viruses are segmented, negative-strand RNA viruses belonging to the family Orthomyxoviridae. Influenza virus hemagglutinin glycoprotein (HA) generally is considered the most important viral antigen with regard to the stimulation of neutralizing antibodies and vaccine design. The presence of viral neuraminidase (NA) has been shown to be important for generating multi-arm protective immune responses against the virus. Antiviral agents that inhibit neuraminidase activity have been developed and can be an additional antiviral treatment upon infection. A third component considered useful in the development of influenza antivirals and vaccines is the ion channel protein M2.
Subtypes of the influenza virus are designated by different HA and NA that are the result of antigenic shift. Furthermore, new strains of the same subtype result from antigenic drift or from mutations in the HA or NA molecules that generate new and different epitopes. Although 15 antigenic subtypes of HA have been documented, only three of these subtypes (H1, H2, and H3) have circulated extensively in humans. Vaccination has become paramount in the quest for improved quality of life in both industrialized and underdeveloped nations. The majority of available vaccines still follow the basic principles of mimicking aspects of infection in order to induce an immune response that could protect against the relevant infection. However, generation of attenuated viruses of various subtypes and combinations can be time consuming and expensive. Along with emerging new technologies, in-depth understanding of a pathogen's molecular biology, pathogenesis, and interactions with an individual's immune system has resulted in new approaches to vaccine development and vaccine delivery. Thus, while technological advances have improved the ability to produce improved influenza antigens vaccine compositions, there remains a need to provide additional sources of protection against to address emerging subtypes and strains of influenza.